Limits...
Absence of Elovl6 attenuates steatohepatitis but promotes gallstone formation in a lithogenic diet-fed Ldlr(-/-) mouse model.

Kuba M, Matsuzaka T, Matsumori R, Saito R, Kaga N, Taka H, Ikehata K, Okada N, Kikuchi T, Ohno H, Han SI, Takeuchi Y, Kobayashi K, Iwasaki H, Yatoh S, Suzuki H, Sone H, Yahagi N, Arakawa Y, Fujimura T, Nakagawa Y, Yamada N, Shimano H - Sci Rep (2015)

Bottom Line: We have previously shown that Elovl6 plays an important role in the development of hepatic insulin resistance and NASH by modifying FA composition.Recent studies have linked altered hepatic cholesterol homeostasis and cholesterol accumulation to the pathogenesis of NASH.The absence of Elovl6 also decreases hepatic inflammation, oxidative stress and liver injury, but increases the formation of cholesterol crystals in the less dilated gallbladder.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

ABSTRACT
Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can develop into liver cirrhosis and cancer. Elongation of very long chain fatty acids (ELOVL) family member 6 (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids (FAs). We have previously shown that Elovl6 plays an important role in the development of hepatic insulin resistance and NASH by modifying FA composition. Recent studies have linked altered hepatic cholesterol homeostasis and cholesterol accumulation to the pathogenesis of NASH. In the present study, we further investigated the role of Elovl6 in the progression of lithogenic diet (LD)-induced steatohepatitis. We showed that the absence of Elovl6 suppresses hepatic lipid accumulation, plasma total cholesterol and total bile acid (BA) levels in LDL receptor-deficient (Ldlr(-/-)) mice challenged with a LD. The absence of Elovl6 also decreases hepatic inflammation, oxidative stress and liver injury, but increases the formation of cholesterol crystals in the less dilated gallbladder. These findings suggest that Elovl6-mediated changes in hepatic FA composition, especially oleic acid (C18:1n-9), control handling of hepatic cholesterol and BA, which protects against hepatotoxicity and steatohepatitis, but promotes gallstone formation in LD-fed Ldlr(-/-) mice.

No MeSH data available.


Related in: MedlinePlus

Attenuated hepatic inflammation and liver injury in lithogenic diet (LD)-fed Elovl6−/−Ldlr−/− mice.(A) Representative hematoxylin and eosin (H&E)-stained sections of livers from Elovl6+/+Ldlr−/− and Elovl6−/−Ldlr−/− mice fed a standard diet (SD) or an LD for 4 weeks. (B) The number of inflammatory foci in H&E-stained sections from each animal at 20× magnification (n = 6–9 per group). (C) Plasma alanine aminotransferase (ALT) levels of Elovl6+/+Ldlr−/− and Elovl6−/−Ldlr−/− mice fed an SD or an LD for 4 weeks (n = 8–13 per group). *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4664962&req=5

f4: Attenuated hepatic inflammation and liver injury in lithogenic diet (LD)-fed Elovl6−/−Ldlr−/− mice.(A) Representative hematoxylin and eosin (H&E)-stained sections of livers from Elovl6+/+Ldlr−/− and Elovl6−/−Ldlr−/− mice fed a standard diet (SD) or an LD for 4 weeks. (B) The number of inflammatory foci in H&E-stained sections from each animal at 20× magnification (n = 6–9 per group). (C) Plasma alanine aminotransferase (ALT) levels of Elovl6+/+Ldlr−/− and Elovl6−/−Ldlr−/− mice fed an SD or an LD for 4 weeks (n = 8–13 per group). *P < 0.05, **P < 0.01.

Mentions: Histological examination of the livers revealed some inflammatory cell infiltration in SD-fed Elovl6+/+Ldlr−/− mice, but not in SD-fed Elovl6−/−Ldlr−/−mice (Fig. 4A). Inflammatory cell infiltration was exacerbated in LD-fed Elovl6+/+Ldlr−/− mice, but markedly ameliorated in LD-fed Elovl6−/−Ldlr−/− mice. The protection from inflammation and liver damage associated with Elovl6 deficiency was reflected in a significantly lower hepatic lobular inflammatory grade (evaluated by the number of inflammatory foci in hematoxylin & eosin [H&E]-stained liver sections) and plasma alanine aminotransferase (ALT) levels in LD-fed Elovl6−/−Ldlr−/− mice compared with LD-fed Elovl6+/+Ldlr−/− mice (Fig. 4B,C).


Absence of Elovl6 attenuates steatohepatitis but promotes gallstone formation in a lithogenic diet-fed Ldlr(-/-) mouse model.

Kuba M, Matsuzaka T, Matsumori R, Saito R, Kaga N, Taka H, Ikehata K, Okada N, Kikuchi T, Ohno H, Han SI, Takeuchi Y, Kobayashi K, Iwasaki H, Yatoh S, Suzuki H, Sone H, Yahagi N, Arakawa Y, Fujimura T, Nakagawa Y, Yamada N, Shimano H - Sci Rep (2015)

Attenuated hepatic inflammation and liver injury in lithogenic diet (LD)-fed Elovl6−/−Ldlr−/− mice.(A) Representative hematoxylin and eosin (H&E)-stained sections of livers from Elovl6+/+Ldlr−/− and Elovl6−/−Ldlr−/− mice fed a standard diet (SD) or an LD for 4 weeks. (B) The number of inflammatory foci in H&E-stained sections from each animal at 20× magnification (n = 6–9 per group). (C) Plasma alanine aminotransferase (ALT) levels of Elovl6+/+Ldlr−/− and Elovl6−/−Ldlr−/− mice fed an SD or an LD for 4 weeks (n = 8–13 per group). *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664962&req=5

f4: Attenuated hepatic inflammation and liver injury in lithogenic diet (LD)-fed Elovl6−/−Ldlr−/− mice.(A) Representative hematoxylin and eosin (H&E)-stained sections of livers from Elovl6+/+Ldlr−/− and Elovl6−/−Ldlr−/− mice fed a standard diet (SD) or an LD for 4 weeks. (B) The number of inflammatory foci in H&E-stained sections from each animal at 20× magnification (n = 6–9 per group). (C) Plasma alanine aminotransferase (ALT) levels of Elovl6+/+Ldlr−/− and Elovl6−/−Ldlr−/− mice fed an SD or an LD for 4 weeks (n = 8–13 per group). *P < 0.05, **P < 0.01.
Mentions: Histological examination of the livers revealed some inflammatory cell infiltration in SD-fed Elovl6+/+Ldlr−/− mice, but not in SD-fed Elovl6−/−Ldlr−/−mice (Fig. 4A). Inflammatory cell infiltration was exacerbated in LD-fed Elovl6+/+Ldlr−/− mice, but markedly ameliorated in LD-fed Elovl6−/−Ldlr−/− mice. The protection from inflammation and liver damage associated with Elovl6 deficiency was reflected in a significantly lower hepatic lobular inflammatory grade (evaluated by the number of inflammatory foci in hematoxylin & eosin [H&E]-stained liver sections) and plasma alanine aminotransferase (ALT) levels in LD-fed Elovl6−/−Ldlr−/− mice compared with LD-fed Elovl6+/+Ldlr−/− mice (Fig. 4B,C).

Bottom Line: We have previously shown that Elovl6 plays an important role in the development of hepatic insulin resistance and NASH by modifying FA composition.Recent studies have linked altered hepatic cholesterol homeostasis and cholesterol accumulation to the pathogenesis of NASH.The absence of Elovl6 also decreases hepatic inflammation, oxidative stress and liver injury, but increases the formation of cholesterol crystals in the less dilated gallbladder.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

ABSTRACT
Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can develop into liver cirrhosis and cancer. Elongation of very long chain fatty acids (ELOVL) family member 6 (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids (FAs). We have previously shown that Elovl6 plays an important role in the development of hepatic insulin resistance and NASH by modifying FA composition. Recent studies have linked altered hepatic cholesterol homeostasis and cholesterol accumulation to the pathogenesis of NASH. In the present study, we further investigated the role of Elovl6 in the progression of lithogenic diet (LD)-induced steatohepatitis. We showed that the absence of Elovl6 suppresses hepatic lipid accumulation, plasma total cholesterol and total bile acid (BA) levels in LDL receptor-deficient (Ldlr(-/-)) mice challenged with a LD. The absence of Elovl6 also decreases hepatic inflammation, oxidative stress and liver injury, but increases the formation of cholesterol crystals in the less dilated gallbladder. These findings suggest that Elovl6-mediated changes in hepatic FA composition, especially oleic acid (C18:1n-9), control handling of hepatic cholesterol and BA, which protects against hepatotoxicity and steatohepatitis, but promotes gallstone formation in LD-fed Ldlr(-/-) mice.

No MeSH data available.


Related in: MedlinePlus